瑞士苏黎世联邦理工学院Barbara Treutlein与德国慕尼黑亥姆霍兹研究所Fabian J. Theis等人合作取得一项新成果。经过不懈努力，他们绘制了人神经类器官的整合转录组细胞图谱。相关论文于2024年11月20日发表在《自然》杂志上。

据介绍，由体外多能干细胞生成的人神经类器官，是研究人类大脑发育、进化和疾病的有用工具。然而，目前还不清楚现有类器官包含了人脑的哪些细胞类型，也很难定量评估类器官的变异和保真度。

研究人员将26个不同方案的36个单细胞转录组数据集，整合到一个总计超过170万个细胞的人类神经类器官细胞图谱中。与发育中人脑参考数据相比较，类器官具有体外生成的原代细胞类型和状态，研究还估算了原代细胞和类器官之间，由方案不同造成的转录组相似性。

该研究提供了浏览图谱和查询新数据集的程序界面，并展示了该图谱在注释类器官细胞类型，和评估新类器官方案方面的强大功能。

最后，研究还表明该图集可作为一个多样化的对照队列，用于注释和比较神经疾病的类器官模型，识别可能造成模型神经疾病的基因和通路。人类神经类器官细胞图谱将有助于评估类器官的保真度、特征紊乱和疾病状态，并促进类器官制备方法的开发。

附：英文原文

Title: An integrated transcriptomic cell atlas of human neural organoids

Author: He, Zhisong, Dony, Leander, Fleck, Jonas Simon, Szaata, Artur, Li, Katelyn X., Slikovi, Irena, Lin, Hsiu-Chuan, Santel, Malgorzata, Atamian, Alexander, Quadrato, Giorgia, Sun, Jieran, Paca, Sergiu P., Camp, J. Gray, Theis, Fabian J., Treutlein, Barbara

Issue&Volume: 2024-11-20

Abstract: Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated human neural organoid cell atlas totalling more than 1.7million cells1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26. Mapping to developing human brain references27,28,29,30 shows primary cell types and states that have been generated in vitro, and estimates transcriptomic similarity between primary and organoid counterparts across protocols. We provide a programmatic interface to browse the atlas and query new datasets, and showcase the power of the atlas to annotate organoid cell types and evaluate new organoid protocols. Finally, we show that the atlas can be used as a diverse control cohort to annotate and compare organoid models of neural disease, identifying genes and pathways that may underlie pathological mechanisms with the neural models. The human neural organoid cell atlas will be useful to assess organoid fidelity, characterize perturbed and diseased states and facilitate protocol development.

DOI: 10.1038/s41586-024-08172-8

Source: https://www.nature.com/articles/s41586-024-08172-8